tbuckley/cabot-search huggingface dataset:
Anlotinib combined with etoposide as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC): Updated results from a phase II trial.
Authors: Bo Shen, Yuan Wu, Lin Shi, Banzhou Pan, Kaihua Yang, Qiong Wang, Weiqing Zhao, Zhengxiang Han, Lifeng Wang, Jifeng Feng
Journal: Journal of Clinical Oncology (2022)

e20610 Background: Existing maintenance treatment strategies for patients with ES-SCLC experiencing no progression after the standard first-line chemotherapy are limited. Anlotinib combined with etoposide as maintenance treatment in ES-SCLC after the standard first-line EP chemotherapy showed encouraging efficacy and good tolerability. This is an update of the phase II study (ChiCTR1800019421). Methods: Patients with histologically confirmed ES-SCLC who have not progressed after the standard first-line EP chemotherapy received anlotinib (12 mg, day 1 to 14 of a 21-day cycle) combined with etoposide (50 mg, QD, day 1 to 14 of a 21-day cycle, up to 6 cycles) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Results: Between April 2019 and October 2021, we screened 31 patients and enrolled 27 patients in this trial. At data cut-off (January 7, 2022), 20 (74%) patients had discontinued the trial, and 7 (26%) patients remained on treatment. The median follow-up time reached 12.9 months. Among 27 evaluable patients, there was 9 partial response, 17 stable disease and 1 disease progression, resulting in the objective response rate 33.3% and disease control rate 96.3%. The median PFS was 8.9 months (95%CI: 5.4-12.3). The median OS was 13.6 months (95%CI: 9.6-17.6). The most common grade 1-2 adverse events (AEs) were anorexia (9 of 27, 33.3 %), hypertension (8 of 27, 29.6 %) and fatigue (7 of 27, 25.9 %). The most common grade 3-4 AEs were anorexia (4 of 27, 14.8%), hypertension (2 of 27, 7.4%) and hand and foot skin reaction (2 of 27, 7.4 %). Nine patients had to adjust treatment dosage. Conclusions: This updated results have confirmed the combination of anlotinib and etoposide showed significant efficacy and favorable safety profile. The combination may represent a new treatment option as maintenance treatment in patients with ES-SCLC having not progressed after the standard first-line EP chemotherapy. The further exploration is ongoing. Clinical trial information: ChiCTR1800019421.
CT scan versus bioelectrical impedance spectrometry sarcopenia assessment to predict chemotherapy toxicity in early breast cancer.
Authors: Gabriel Aleixo, Stephanie A. Valente, Wei Wei, Po-Hao Chen, Halle C. F. Moore
Journal: Journal of Clinical Oncology (2022)

12078 Background: There is growing literature on the impact of the progressive loss of skeletal muscle known as sarcopenia in women with early breast cancer (EBC). Imaging techniques such as Computed Tomography (CT) scans are the most studied methods to detect sarcopenia in patients with cancer; however, most patients with EBC do not require routine CT scans. Bioelectrical impedance spectrometry (BIS) is a method that does not expose patients to radiation and provides measurements to assess sarcopenia instantaneously. The extent to which BIS-assessed sarcopenia correlates with CT-assessed sarcopenia is uncertain. It is also unclear whether sarcopenia detected with either method can be associated with chemotherapy tolerance To address these questions, we evaluated the correlation between CT and BIS sarcopenia and associations of sarcopenia by each method with chemotherapy related outcomes in patients with EBC. Methods: This retrospective study identified patients with EBC who received chemotherapy (ACT, TC, TH, THP), underwent BIS analyses (ImpediMed) at any point between diagnosis and treatment completion and also received a CT abdomen including L3 level. Axial CT L3 segments were analyzed using Slice-O-Matic software. CT L3, and BIS generated the Skeletal Muscle (SM). Skeletal Muscle Index (SMI) was then calculated to assess for sarcopenia: BIS SMI= (SM in kg)/ (patient height, m2) and CT L3 SMI (SM cm2/ height m2). Patients were divided into normal SMI, and sarcopenia (if BIS was used SMI &lt;6.75 kg/m2 and if CT SMI &lt;40 cm2/m2). Patient medical records were reviewed for patient characteristics, grade 3 and 4 toxicity, including neuropathy symptoms, chemotherapy dose reductions, early treatment discontinuation or need for hospitalization during chemotherapy treatment. Spearman's rank coefficient was used to assess the correlation between CT SMI and BIS SMI. Multivariable logistic regression was used to associate sarcopenia with outcomes, controlling for age and BMI. Results: 361 patients received chemotherapy, underwent BIS; of those 171 had L3 CT scans. The correlation between L3 CT SMI and BIS SMI was r= 0.64 p&lt;0.0001. In the multivariable model, sarcopenia assessed by L3 CT scan was associated with chemotherapy dose reduction (CI 0.04-0.60 p=0.01) and neuropathy (CI 0.10-0.95 P=0.04) but not with grade 3 or 4 chemotherapy toxicity (CI 0.13-1.09 p=0.07), early treatment discontinuation (p=0.3) or hospitalization (p=0.60). Sarcopenia assessed by BIS was associated with grade 3 or 4 chemotherapy toxicity (CI 0.2-0.83 p=0.01), neuropathy (CI 0.1-0.51 p=0.0003), early treatment discontinuation (OR 0.26 CI 0.11-0.80 p=0.001), and hospitalization (CI 0.12-0.68 p=0.004). Conclusions: There is a strong correlation between L3 CT scan and BIS screened sarcopenia in patients with EBC. Sarcopenia detected with either CT L3 or BIS is associated with worse chemotherapy tolerance.
An observational study of dose-optimization for fruquintinib in elderly patients (pts) with metastatic colorectal cancer (mCRC) who had failed standard therapy.
Authors: Hongfeng Gou, Jing Yu, Xiaohong Cai, Qiu Li
Journal: Journal of Clinical Oncology (2022)

e15560 Background: As one of the third-line standard treatment regimens for advanced colorectal cancer, fruquintinib is widely used in clinical practice, but there are limited data on safety and efficacy of fruquintinib in elderly pts. Multiple studies have shown improved tolerability, reduced grade 3-4 adverse events, and comparable efficacy in pts treated with regorafenib through a first-cycle flexible dose optimization regimen. This method of drug administration is more practical especially in elderly pts, and is worthy of clinical adoption. This observational study aims to investigate the safety, tolerability, and efficacy of a dose-optimized regimen of fruquintinib in elderly mCRC pts who had failed previous standard therapy. Methods: Pts ≥65 years with mCRC refractory to fluoropyrimidine-based chemotherapy ± anti-VEGF/EGFR were enrolled. The primary endpoint was progression-free survival (PFS) (RECIST v1.1). All pts were administered with fruquintinib 3mg (po, qd) for one week. If tolerable, fruquintinib 4mg would be administered in the second week. In the third week, fruquintinib 5mg would be administered if 4mg is tolerable, followed by a week’s rest. The maximum tolerated dose (MTD) of fruquintinib confirmed in the first cycle would be administered from the second cycle. Adverse events were evaluated using CTCAE 5.0. Results: As of February 9, 2022, 29 pts were identified, with an median age of 69.59 (65-77) years and 16 males (55.2%) included. Of the 29 pts, the MTD was 3mg in 31% (9/29) pts, 4mg in 58.6% (17/29) pts and 5mg in 10.3% (3/29) pts. Among the 24 pts available for efficacy evaluation, 14 had stable disease (SD) and 10 had progressive disease (PD) as the best response. Disease control rate (DCR) of 3mg group, 4mg group and 5mg group were 33.33% (2/6), 68.75% (11/16) and 50.00% (1/2), respectively. At a median 4.93 months follow-up, the median (m) PFS was 3.73 months [95% CI, 2.32-5.14] and the mOS was 7.97 months [95% CI, 5.05-10.89]. In addition, the median PFS of 3mg group and 4mg group were 1.87 months and 3.73 months, respectively. And the median OS of 3mg group and 4mg group was 7.97 months and 11.0 months, respectively. Treatment-related adverse events (TRAEs) were observed in all 29 pts (100%). Common TRAEs (&gt; 40%) included fatigue (79.3%), anorexia (58.6%) and hand-foot syndrome (44.8%). The most common (&gt; 10%) grade≥3TRAEs were hand-foot syndrome (20.7%), hypertension (17.2%) and diarrhea (10.3%). No grade 5 TRAEs were observed. There were no correlations with efficacy, toxicity, and geriatric assessment scores. Conclusions: The dose-optimized strategy of fruquintinib in pts aged ≥ 65 years showed acceptable toxicities and anti-tumor activities consistent with the overall population in FRESCO study. The dose-optimized strategy of fruquintinib is a viable alternative in older pts with mCRC. Clinical trial information: NCT05025631.
AGO-OVAR 28/ENGOT-ov57: Niraparib versus niraparib in combination with bevacizumab in patients with carboplatin-taxane based chemotherapy in advanced ovarian cancer—A multicenter, randomized, phase III trial.
Authors: Florian Heitz, Christian Marth, Stephanie Henry, Alexander Reuss, David Cibula, Lydia Gaba, Nicoletta Colombo, Sandra Polleis, Philipp Harter
Journal: Journal of Clinical Oncology (2022)

TPS5612 Background: Standard of care chemotherapy in patients (pts) with advanced ovarian cancer (AOC) is the combination of carboplatin and paclitaxel. Data from the PRIMA trial has shown a significant benefit in pts by the addition of a maintenance treatment (MT) with niraparib irrespective of BRCA or HRD-status in high-grade ovarian cancers (OC). The PAOLA-1 trial evaluated MT in pts with AOC with the combination of olaparib and bevacizumab and has also shown a significant benefit compared to bevacizumab monotherapy. However, it is unclear if a PARP-inhibitor (PARPi) MT monotherapy is sufficient or if the addition of bevacizumab is needed. Therefore, we investigate, if the treatment strategy of carboplatin / paclitaxel / bevacizumab / PARPi is superior to the treatment of carboplatin / paclitaxel / PARPi in an all-comer population. Methods: AGO-OVAR 28/ ENGOT-ov57 (NCT05009082; EudraCT Number: 2021-001271-16) is an Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) Study Group led, international, multicenter, randomized, prospective phase III trial within the ENGOT trial network. The trial population is composed of adult pts with newly diagnosed, advanced high-grade epithelial OC, primary peritoneal cancer or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). All pts should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of Study Run-In-Period. Prior to day1 of cycle2, pts with a valid central tumor BRCA ( tBRCA) test result will be randomized 1:1 into either Arm1 and will receive 5 additional cycles of carboplatin and paclitaxel, q21d followed by niraparib for up to 3 years; or into Arm2 where pts will receive 5 additional cycles of carboplatin and paclitaxel plus bevacizumab, q21d followed by bevacizumab, q21d (for up to 1 year) and niraparib for up to 3 years. Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also allowed to be included in the trial. The primary objective is progression free survival (PFS). Secondary objectives include but are not limited to: PFS according to tBRCA-status, overall survival, PFS2, safety and tolerability, and quality of life. The trial will start in Q1/2022 with First Patient First Visit expected in Q2/2022. It is planned to recruit 970 patients. Clinical trial information: NCT05009082.
Alkaline phosphatase (ALP) decline and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) treated with radium-223 (Ra-223) in the REASSURE study.
Authors: Nicholas D. James, Daniel Heinrich, Elena Castro, Saby George, Daniel Y. Song, Sabina Dizdarevic, Sergio Baldari, Markus Essler, Igle Jan de Jong, Secondo Lastoria, Peter G. Hammerer, Jeffrey Meltzer, Per Sandstrom, Frank Verholen, Bertrand F. Tombal, Joe M. O'Sullivan, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2022)

5041 Background: Ra-223 extends OS in pts with mCRPC. Predictive markers of response to Ra-223 are needed to help select pts who would benefit most from Ra-223 therapy. The ALSYMPCA study suggested a correlation between ALP decline and longer OS. Here, we evaluated whether ALP decline is associated with OS in the global real-world REASSURE study. Methods: Pts treated with Ra-223 were grouped by baseline ALP ≤147 U/L vs &gt;147 U/L and any ALP decline vs no decline at week 12 from the first Ra-223 dose. The 147 U/L cut-off was selected based on the highest upper limit of normal for ALP from literature. Pts with a trend of decreasing ALP at closest value to week 12 between weeks 8 and 16 were included in the any decline group. Association of ALP decline with OS was assessed in the ≤147 U/L and &gt;147 U/L groups separately. Median OS is provided with an unadjusted hazard ratio (HR) (95% confidence interval [CI]). Multivariate Cox models provided adjusted HRs (95% CI) for the association of ALP decline with OS. Some baseline covariates were not included in the models due to missing data. Results: 785 of 1465 pts had baseline ALP measurements, of whom 779 had week 12 ALP measurements: 443 had ≤147 U/L and 336 &gt;147 U/L. In the ≤147 U/L group, median OS was 23.0 months (m) (95% CI 20.9–25.7) in pts with ALP decline (n=329) and 16.4 m (95% CI 14.1–20.4) in pts with no decline (n=114). In the &gt;147 U/L group, median OS was 12.9 m (95% CI 11.7–14.3) in pts with ALP decline (n=295) and 8.1 m (95% CI 5.6–10.3) in pts with no decline (n=41). Comparison of unadjusted and adjusted HRs is shown in the Table. Conclusions: Pts with an ALP decline in first 12 weeks of Ra-223 treatment had longer OS. The effect of other baseline variables, including age, PSA, Hgb and prior treatments, provided adjustment but did not change this outcome. [Table: see text]
Updated survival with extended follow-up on patients with newly diagnosed multiple myeloma treated with lenalidomide, bortezomib, and dexamethasone (RVD) induction therapy and a risk-stratified maintenance approach.
Authors: Rujul H Parikh, Craig C. Hofmeister, Dhwani Almaula, Leonard T. Heffner, Vikas Anand Gupta, Lawrence Boise, Jonathan L. Kaufman, Madhav V. Dhodapkar, Sagar Lonial, Ajay K. Nooka, Nisha Joseph
Journal: Journal of Clinical Oncology (2022)

8061 Background: Lenalidomide, bortezomib, and dexamethasone (RVD) has been established as an effective and well-tolerated induction regimen in patients with newly diagnosed myeloma (NDMM). We have previously published a retrospective analysis of 1000 patients treated with RVD and risk-stratified maintenance therapy showing a median PFS of 65 months and median OS of 126 months for the entire cohort (Joseph et al, JCO 2020). This data has served as an important benchmark for evaluating upfront treatment strategies in NDMM. Here, we present updated survival data with extended follow up on this patient population treated at the Winship Cancer Institute of Emory University. Methods: From January 2007 to August 2016, 1000 consecutive newly diagnosed myeloma patients treated with RVD induction therapy (R-25 mg/day on days 1-14, V-1.3 mg/m2 on days 1,4,8,11 and D-40 mg once/twice weekly as tolerated) were identified. Demographics, clinical characteristics, and outcomes data for the patients were obtained from our institutional review board-approved myeloma database. Responses were evaluated per IMWG Uniform Response Criteria. Results: The median age of this cohort was 61 (range 16-83). Other notable patient characteristics include: M/F 54.6%/45.4%, W/AA 61.8%/35.9%; ISS I/II/III 45.8%/30.8%/23.4%. R-ISS I/II/III 39.9%/48.7%/11.5%; Isotype IgG/IgA/FLC 59.2%/19.0%/15.7%; standard risk(SR)/high risk (HR) 71.2%/15.8%.. High risk disease was defined as the presence of t(4;14), t(14;16), del(17p), and/or complex karyotype by conventional metaphase cytogenetics. 81.8% of patients underwent ASCT, with 16.8% having deferred ASCT. 75.3% of patients were initiated on maintenance therapy. With a median follow up of 88.4 months, the median PFS for the entire cohort was 68.7 months (95% CI 61.8-75.5) and the median OS was 128.9 months. The median PFS for HR patients was 42.4 months (95% CI 35.7-48.9), and the median PFS for SR patients was 80.3 months (95% CI 72.8-87.8). The median OS for SR patients was not reached, and for HR patients was 86.6 months (95% CI 70.1-103.1). Conclusions: Updated analysis with long-term follow up of this database of 1000 NDMM patients treated with RVD continues to demonstrate that, in combination with a risk-stratified maintenance strategy, RVD delivers durable remissions and impressive long-term outcomes. This study remains the largest cohort of patients treated with RVD reported to date, and continues to show the efficacy of this upfront treatment approach in newly diagnosed myeloma.
Detection of early-stage ovarian cancer using a liquid biopsy test based on extracellular vesicle proteins.
Authors: Juan Pablo Hinestrosa, Jean Lewis, Gregor Schroeder, Heath Balcer, Paul R. Billings
Journal: Journal of Clinical Oncology (2022)

e17558 Background: We have recently conducted a study to evaluate the predictive value of proteins associated with extracellular vesicles (EVs) isolated using an alternating current electrokinetic (ACE) system, for the detection of early stage (I &amp; II) ovarian cancer cases. Ovarian cancer patients, typically, have few symptoms in stages I &amp; II; the disease is often undetected until it is advanced. Currently, only 15% of cases are detected at early stages when clinical treatment outcomes are improved. Methods: We tested the feasibility of detecting the presence of early stage (I-II) ovarian cancer using protein biomarkers carried by EVs in patient blood. Using an ACE microelectrode array, EVs were purified from ovarian cancer patient plasma (N = 70; Stage I = 51, Stage II = 19) and female non-cancer donors (N = 290) and tested for the presence of cancer biomarker proteins with multiple bead-based multiplex immunoassay kits. An adaptive boosted trees machine learning algorithm with 100x cross-validation was developed to identify the most important features for differentiation between cases and controls. Results: The machine learning algorithm identified relevant biomarkers for the detection of ovarian cancer with a receiver-operator characteristic area under the curve (AUC) of 0.952 (95% CI: 0.918 – 0.985). Overall sensitivity was 72.9% at 99% specificity, rising to 84.3% at 95% specificity. When further stratified, Stage I sensitivity was 70.6% and stage II sensitivity was 78.9% at the 99% specificity level, as expected. We also separated the cases into endometroid carcinoma (N = 24) and serous carcinoma (N = 36). At the 99% specificity level, the sensitivity was 87.5% and 63.9%, respectively. Conclusions: These results suggest that it is possible to detect early-stage ovarian cancer by analyzing the EV-bound proteins isolated with the ACE technology. EVs may carry the earliest signals of cancer development and a blood-based EV-protein biomarker test can yield high sensitivity and specificity. Stable biomarker detection with small input volumes may be possible. These results require further investigation in larger datasets to validate the current observations with the potential application for general, routine screening, as well as for populations at elevated disease risk.
Lung cancer risk in persons enrolled in low-dose CT screening (LDCT) versus incidental lung nodule programs (ILNP).
Authors: Wei Liao, Nicholas Faris, Carrie Fehnel, Jordan Goss, Alicia Pacheco, Paul F Pinsky, Matthew Smeltzer, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2022)

8553 Background: LDCT screening saves lives, but &lt;10% of eligible persons participate; eligibility criteria are imperfect; geographic, racial and socio-economic disparities have emerged. ILNP may expand access to early detection. We compared rates of lung cancer diagnosis in LDCT and ILNP population subsets. Methods: Prospective observational cohort study of enrollees in LDCT and ILNP in a community healthcare system in AR, MS and TN. We compared LDCT vs 4 ILNP cohorts (C) based on USPSTF 2021 LDCT eligibility criteria: &lt;50 years (C1, too young); &gt;80 years (C2, too old); 50 – 80 years (C3, ineligible smoking history); 50 – 80 years (C4, eligible). For certain analyses, we stratified the LDCT cohort by baseline (T0) Lung-RADS score (0-2 v 3-4). We used a Cox model to calculate crude and adjusted hazard ratios (aHR) for lung cancer diagnosis within 24 months of enrollment. Results: From 2015-2021, 7050 persons were in LDCT- 6073 (86%) Lung-RADS 0-2 (no/benign lesions), 977 (14%) Lung-RADS 3 or 4 (possibly malignant lesion) on T0 scan; 17,579 were in ILNP, 16%, 10%, 57% and 16% respectively in C1-4. Demographics and tobacco use history of the ILNP cohorts differed strikingly; C4 was very similar to LDCT (Table). Black persons were significantly more in C1 (too young) and C3 (insufficient tobacco use). Diagnosis of lung cancer at 36 months ranged from 1% in C1 to 15% in C4, compared to 3% in LDCT; aHR for lung cancer diagnosis within 2 years ranged from 0.23 to 5.12 (all LDCT ref), but ranged from 0.04 to 1.02 with reference to LDCT Lung-RADS 3-4. Most patients in LDCT and ILNP C2-4 had early stage. There were proportionately more Black lung cancer patients in C1-4, and 3 times more Black patients in C3 and 4 than in LDCT. Conclusions: ILNP provides early-detection access to a larger, more diverse population than LDCT, potentially alleviating race and socio-economics-based outcomes disparities. [Table: see text]
Predictive factors of recurrence of urethral strictures after a first internal uretrotomy
Authors: S. Zouari, A. Saadi, M. Chakroun, S. Zaghbib, N. Setti Boubaker, H. Boussaffa, A. Bouzouita, A. Derouiche, R. Ben Slama, H. Ayed, M. Chebil
Journal: European Urology (2022)
Re: Deepika Reddy, Max Peters, Taimur T. Shah, et al. Cancer Control Outcomes Following Focal Therapy Using High-intensity Focused Ultrasound in 1379 Men with Nonmetastatic Prostate Cancer: A Multi-institute 15-year Experience. Eur Urol 2022;81:407–13
Authors: Francesco Montorsi, Armando Stabile, Elio Mazzone, Giorgio Gandaglia, Alberto Briganti
Journal: European Urology (2022)